A beneficial role for vitamin D in prostate cancer survivors is supported by anticancer effects consistently shown in both in vitro and in vivo studies, and by observational research reporting inverse associations between sunlight exposure and prostate cancer mortality. Vitamin D analogs have also shown therapeutic efficacy in selected patients. However, few epidemiological studies have specifically evaluated circulating vitamin D levels in relation to prostate cancer prognosis. This study will investigate whether plasma concentration of 25-hydroxyvitamin D [25(OH)D] in men diagnosed with prostate cancer is associated with disease outcomes. The study has the following specific aims: 1) To measure plasma concentration of 25(OH)D in a population-based cohort of prostate cancer cases;and, 2) To evaluate the association between plasma 25(OH)D concentrations with risks of prostate-cancer specific death and tumor recurrence or progression. To accomplish these aims we will build upon an existing population-based cohort of 1,477 histologically confirmed prostate cancer cases (with 6-18 years of follow-up) for which extensive epidemiological data, clinical data, post-diagnosis blood samples, and genetic variation in vitamin D metabolism genes (VDR, CYP27B1 and CYP24A1) have already been collected or measured. This unique cohort is under on-going follow-up for ascertainment of disease recurrence/progression, vital status and underlying cause of death (funded by a separate grant). Adjusted Cox proportional hazards regression models will be used to determine hazard ratios and 95% confidence intervals for the outcomes according to vitamin D level. We will also explore if these hazard ratios are modified by body mass index, race, or vitamin D metabolism genotypes. Associations also will be examined within patient subgroups defined by clinical parameters known to influence prostate cancer outcomes (Gleason score, tumor stage, diagnostic PSA level) and by primary treatment. Only one small epidemiological study has previously reported a positive association between serum concentration of 25(OH)D and prostate cancer survival. The proposed study will be the largest study to date to evaluate vitamin D level in prostate cancer survivors, and will include analyses of additional endpoints and evaluation of relevant subgroups. This innovative and cost-effective application to relate plasma vitamin D status with patient prognosis could provide evidence supporting the use of vitamin D level as a biomarker for identifying men at higher risk for adverse outcomes and bolster efforts to develop a vitamin D analog as a therapeutic agent for appropriate patients where vitamin D may have the greatest impact on prognosis. PUBLIC HEALTH RELEVANCE: Project Narrative In 2009 there will be an estimated 27,360 deaths from prostate cancer and a significant additional burden to the U.S. in terms of disease morbidity and health care costs for the 192,280 men diagnosed with prostate cancer. This study will measure vitamin D, a modifiable factor with demonstrated anti-cancer effects, in the plasma of men with prostate cancer and estimate the risks of cancer recurrence/progression and prostate cancer-specific death by vitamin D levels. Results from this study could be used to design clinical trials exploring the potentially beneficial effects of vitamin D in the treatment of certain patient populations with prostate cancer, thereby improving patient prognosis, and to develop vitamin D as a potential biomarker for patients with more aggressive disease.